Clinical Research Directory

Group-Based Intervention to Improve Mental Health and Adherence Among Youth Living With HIV in Low Resource Settings

IMPAACT 2016 was a multi-site, two-arm, individually randomized, controlled study to evaluate whether an Indigenous Leader Outreach Model (ILOM) of trauma-informed cognitive behavioral therapy (TI-CBT) delivered by Indigenous Youth Leaders (IYL) is associated with improved mental health outcomes and ART adherence among youth living with HIV in resource-limited settings. The intervention was adapted to the local context through advance conduct of focus groups and pilot testing.

Study of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living With HIV-1, Two to Less Than 12 Years of Age

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, tolerability, and acceptability of a long-acting injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living with HIV-1, Two to Less Than 12 Years of Age

Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV

People with HIV experience earlier impairments in physical function compared to people in the general population. They also exhibit an earlier presentation and more rapid development of frailty, a multisystemic syndrome of aging characterized by reduced activity, fatigue, slowness, weakness, and weight loss. While exercise can improve physical function in people with HIV, it is less effective in doing so than in the general population and is difficult to sustain in the long-term. The goal of this clinical trial is to learn whether the medication tesamorelin will improve physical function and muscle health in adults with HIV when combined with exercise. Tesamorelin is a growth hormone-releasing hormone analogue that is FDA-approved to treat abdominal fat accumulation in people with HIV. While tesamorelin has also been shown to increase muscle mass and improve measures of muscle health, its effects on physical performance and muscle strength have not yet been evaluated. During a 24-week intervention phase, half of participants will be randomly assigned to receive tesamorelin and half of participants will be randomly assigned to receive placebo (a look-alike substance that contains no drug). All participants also will engage in a home-based exercise intervention supervised by an exercise coach. During a subsequent 24-week extension phase, individuals will be monitored off study drug and supervised exercise, and be encouraged to continue to exercise independently. The investigators will investigate effects of tesamorelin on physical function, muscle mass and quality, quality of life, and exercise adherence and self-efficacy. They also will evaluate whether effects of tesamorelin are maintained following treatment cessation. This study may identify an important strategy to improve how individuals aging with HIV function and feel with potential applications to other patient populations.

Study of GS-3242 in Participants With HIV-1; Substudy-05

This study is part of a master study. The goal of master protocol (GS-US-544-5905, NCT05585307) is to learn how novel antiretrovirals (medicines that stop the virus from multiplying) affect the human immunodeficiency virus-1 (HIV-1) infection in people living with HIV (PWH). Substudy GS-US-544-5905-05 is to learn more about the study drug GS-3242 in PWH.

A Clinical Trial of STP0404 in Adults With HIV-1 Infection

The purpose of this study is to evaluate the antiviral effect, safety, tolerability, and pharmacokinetics of STP0404 in adult participants living with Human Immunodeficiency Virus Type 1 (HIV-1) infection.

BCG Vaccination Effect on Latent Reservoir Size in Treated HIV-1 Infection:

A phase IIA randomized double-blind placebo-controlled single-centre study of the effect of Bacillus Calmette-Guérin (BCG) vaccination on the HIV latent reservoir

Cannabis Use, Cognition, and the Endocannabinoid System in HIV

Understanding how co-morbidities in persons with HIV (PWH) such as substance use affect risk-taking, decision-making, and other cognitive behaviors is important given implications for everyday functioning and transmission risk. The high prevalence of cannabis use in PWH, medicinally and recreationally, may indicate disease severity, impart therapeutic benefits, or adverse consequences. In fact, cannabis is recommended to those with HIV to alleviate nausea, improve appetite, relieve pain, and lift mood. To-date, the consequences of cannabis use in PWH remain unclear as do potential interactions with HIV treatments. In healthy participants, heavy cannabis use is associated with cognitive deficits e.g., risky decision-making, response disinhibition and inattention, but pro-cognitive effects in PWH may exist at mild use levels due to its anti-inflammatory and anti-excitotoxic properties. Furthermore, little has been done to determine the effects of cannabis use on the endocannabinoid (EC) system in general or in PWH. This study will determine the effects of the two primary cannabis constituents (Δ9-tetrahydrocannabinol \[THC\], cannabidiol \[CBD\]) vs. placebo on risky decision-making, response inhibition, reward learning, temporal perception, and motivation, plus EC and homovanillic acid (HVA; a surrogate for dopamine activity) levels in HIV+ and HIV- subjects. Participants with infrequent cannabis use will undergo baseline cognitive testing and biomarker assays with antiretrovirals (ART) use quantified. They will be randomized to a 5-day course of either THC, CBD, or placebo and return for follow-up testing and re-assaying of ECs and HVA levels.

Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1

The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels \< 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening. The primary objective is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 48.

Comparing Immune Activation and Latent HIV Reservoir Size Between People Living With HIV on Tenofovir-containing Versus NRTI-free ART

The goal of the project is to determine the difference in immune activation and HIV reservoir size between People living with HIV (PWH) on tenofovir-containing antiretroviral therapy (ART) versus PWH on nucleoside reverse transcriptase inhibitor (NRTI)-sparing ART. Tenofovir (TFV), a phosphonated nucleoside reverse transcriptase inhibitor (NRTI), is being used for oral pre-exposure prophylaxis (PrEP). The investigators will test this hypothesis: tenofovir, and perhaps NRTIs in general, stimulate a type I/III interferon also in PWH who take these drugs. Because chronic interferon stimulation may promote the survival and proliferation of cells with integrated provirus, the investigators also hypothesize that these drugs antagonize decay of the HIV latent reservoir in PWH on ART. Consequently, the researchers hypothesize that PWH who have switched from NRTI-containing ART to NRTI-sparing ART exhibit lower type I/III interferon pathway activation and lower latent HIV reservoir size. The investigators also hypothesize that independently of treatment, the extent of type I/III interferon activation correlates with latent HIV reservoir size. Thus, the proposed study seeks to answer these two questions. Can the gastrointestinal epithelium be impacted by ART, and contribute to chronic immune activation and expansion of the HIV-1 reservoir? If so, what therapeutic approaches can the investigators implement to reduce the HIV-1 proviral load? The data will reveal pathways that can be targeted therapeutically to treat chronic immune activation in PWH. The findings of this study will immediately translate to optimize the standard of care in PWH.

Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV

The prevalence of obesity is rising worldwide, both in low- and high-income countries, including people with HIV (PWH). Semaglutide's efficacy in achieving weight loss in obese PWH is still unexplored. The aim of this study is to assess the efficacy and safety of semaglutide in achieving greater weight loss compared to diet and excercise alone in obese PWH and to explore the effect of semaglutide on the immune function, markers of immune activation, viral reservoir, markers of glucose and lipid metabolism and gut microbiome.

10E8.4/iMab Bispecific Antibody and VRC07-523LS Monoclonal Antibody in HIV-infected Adults

This is an open-label phase 1b clinical trial enrolling people living with HIV (PLWH) who are antiretroviral therapy (ART)-naïve or have not been on ART for \> 24 weeks. This study will enroll PLWH to assess the safety, tolerability, and antiviral effect of bispecific and long-acting bNAbs, alone and in combination. The study will be conducted as a single center study at National Institute for Medical Research-Mbeya Medical Research Center (NIMR-MMRC) in Mbeya, Tanzania. 20 PLWH will be sequentially enrolled into one of 5 arms, each arm comprised of 4 participants. Sequential enrollment will occur in the following order: * Arm 1 will receive standard daily oral ART. * Arm 2 will receive a single dose of 10E8.4/iMab 600mg intravenous injection (IV). * Arm 3 will receive a single dose of 10E8.4/iMab 600mg intramuscular injection (IM). * Arm 4 will receive a single dose of 10E8.4/iMab 1800mg IV. * Arm 5 will receive a single dose of combination therapy with both 10E8.4/iMab 1800mg IV and VRC07-523LS 1200mg IV.

Evaluation of Long-Acting Lenacapavir for the Treatment of HIV-1 in Treatment-experienced Adolescents and Children

The goal of this clinical study is to learn more about the study drug, lenacapavir (LEN). The study will assess the safety, tolerability, and efficacy of long-acting LEN when combined with other medicines in adolescents and children living with HIV-1 who weigh at least 35 kg and have been treated before for HIV-1. The study will also see how easy it is for participants to take LEN as injection or an oral pill. The primary objectives are to evaluate the pharmacokinetics and safety of LEN in combination with optimized background regimen (OBR) in TE pediatric participants with HIV-1.

Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Newborns Exposed to HIV

The goal of this clinical study is to learn more about the study drug, Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), safety, tolerability, and pharmacokinetics (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) in neonates exposed to human immunodeficiency virus type 1 (HIV-1). The primary objective of this study is to evaluate the safety and plasma pharmacokinetics (PK) (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) of B/F/TAF tablet for oral suspension (TOS) in full-term neonates exposed to HIV-1 but uninfected.

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated

The goal of this clinical study is to learn more about the experimental drugs lepetegravir (formerly GS-1720) (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and lenacapavir pacfosacil (formerly GS-4182) (a prodrug of Lenacapavir (LEN)); to compare the combination of lepetegravir and lenacapavir pacfosacil with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of lepetegravir and lenacapavir pacfosacil is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH). This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of oral weekly lepetegravir coadministered with lenacapavir pacfosacil versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase 3: To evaluate the efficacy of oral weekly lepetegravir/lenacapavir pacfosacil fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.

Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV

The clinical study is designed to evaluate the ability of two priming vaccine regimens to activate and induce the maturation of cross-reactive CD4 binding site (CD4-bs) antibodies, including VRC01-class antibodies. VRC01- class antibodies are highly desirable to elicit via vaccination because they have broad cover all clades of HIV and passive administration of VRC01 monoclonal antibodies has been demonstrated to prevent acquisition of susceptible HIV strains in clinical trials. The study will assess whether B cells expressing VRC01-like B cell receptors proliferate following immunization with a 'germline-targeting' recombinant Env immunogen. The study will also test whether an immunization strategy based upon fractionated dose delivery of the immunogen may improve the maturation of VRC01-class B cells when compared to traditional bolus dosing. In addition, the study will test whether alterations in the dose of the subsequent boost immunizations affects VRC01-class B cell activation and the rate of antibody affinity maturation. The primary hypothesis of the optional boost regimen is that BG505 SOSIP.GT1.1 gp140 adjuvated with 3M-052-AF + Alum is safe and well-tolerated and will further mature B-cell lineages elicited by 426c.Mod.Core-C4b priming regimens.

B/F/TAF to DTG/3TC Switch Study

OBJECTIVE: To assess the efficacy and safety of switch to dolutegravir and lamivudine (DTG/3TC) single tablet regimen from bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in persons living with HIV aged 60 years old or more. METHODS: This is a phase 3b, multi-center, open-label, single-arm clinical trial over 96 weeks. The study will take place at two sites in Kenya: Kenyatta National Hospital (KNH) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Study visits will take place at screening, baseline, and weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 (with a 6-week extension as required for confirming HIV-1 RNA levels). A target of 240 participants from the ongoing B/F/TAF Elderly Switch Study will be enrolled. Eligible participants will be switched from B/F/TAF to DTG/3TC at enrollment and followed up for 96 weeks. The primary endpoint will be the proportion of participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at Week 48. Analysis of the primary endpoint will be performed for the intention to treat - exposed (ITT-E) population using the FDA snapshot method.

Pausing Antiretroviral Treatment Under Structured Evaluation

The main purpose of this study is to see if it is safe to give the study antibodies (3BNC117-LS-J and 10-1074-LS-J) by intravenous infusion to people with HIV (PWH), and to see if they cause any side effects. In addition, to see how the study antibodies affect the level of HIV in the blood when participants are not taking regular HIV treatment for an extended period. This extended period of not taking regular HIV treatment is called an analytical treatment interruption (ATI).

A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Initiated ART During Acute/Early HIV-1 Infection

The purpose of this study is to evaluate the safety, tolerability, and efficacy of combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Addressing Barriers to Anti-hypertensive Medication Adherence Among PLWH Who Have Achieved Viral Suppression

Among those with hypertension, persons living with HIV (PWH) have a 50% higher risk of incident myocardial infarction compared to the general population, and they often fail to meet evidence-based treatment goals for hypertension. An important contributing factor for insufficient blood pressure control is non-adherence to antihypertensive medications. Research on medication adherence for PWH has largely focused on antiretroviral therapy adherence with limited focus on adherence to other non-AIDS condition medications. With a large proportion of PWH in the U.S. achieving viral suppression, providers may now have an opportunity to focus on the management of non-AIDS conditions like hypertension. However, because PWH who have achieved suppression have reduced clinic encounters (once or twice a year) there is potential loss of opportunity to effectively monitor and intensify hypertension treatment as needed an important opportunity to focus on preventing cardiovascular disease. CVD and other non-AIDS comorbidities. The study's overarching goal is to improve the hypertension outcomes for PWH on suppressive ART to reduce cardiovascular disease risk. In this study, we will identify and evaluate healthcare and patient-level factors that must be addressed in an intervention to increase hypertension medication adherence for PWH who have achieved viral suppression. We will use these factors to tailor an intervention and assess the feasibility and acceptability at the Duke ID clinic.

Understanding Practices of Lactation and Infant Feeding Together With Women With HIV in the United States

IMPAACT 2046/UPLIFT (Understanding Practices of Lactation and Infant Feeding decisions Together with women with HIV) is a multi-site, mixed-methods, observational cohort study. The purpose of the study is to explore infant feeding preferences, practices, and outcomes among mothers with HIV and their families in the United States. It will employ both qualitative and quantitative research methods to address existing knowledge gaps and to understand the clinical, behavioral, and social factors influencing infant feeding decisions. As part of the study's mixed method approach, a longitudinal cohort study of mothers and their infants will be established. The study also aims to pilot a national registry of breastfeeding women living with HIV in the United States.

A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events. The primary objectives of this study are as follows: * To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment. * To evaluate the safety of the study drug(s) in participants with HIV-1.

Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance

The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen for 14 days (functional monotherapy) in people with human immunodeficiency virus type 1 (HIV-1) (PWH) with multi-drug resistance (MDR).

Simplifying Treatment and Monitoring for HIV (STREAM HIV)

This study seeks to determine the clinical efficacy and cost effectiveness of implementing an integrated model for HIV monitoring using point of care (POC) tenofovir (TFV) adherence testing and POC viral load (VL) monitoring in improving ART adherence, maintaining durable VL suppression, and improving retention in care among HIV-positive individuals initiating first-line tenofovir disoproxil fumarate (TDF)-based ART in South Africa.

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1

The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).